Abstract: Objective　To explore the clinical and genetic characteristics of pediatric monogenic diabetes caused by INS gene mutations in order to establish a foundation for precise diagnosis and treatment. Methods　A retrospective analysis was conducted on the clinical data and gene sequencing results of 11 children diagnosed with diabetes caused by INS gene mutations at Children’s Hospital of Nanjing Medical University from January 2013 to December 2024，and the association between genotype and phenotype was analyzed. Results　Of the 11 cases，9 were male and 2 were female，with a median onset age of 0.75 years（ranging from 0.25 to 14 years）. The 6 patients with infantile onset（<1 year）all presented with ketosis/diabetic ketoacidosis at the first onset and required insulin therapy. Among 5 cases of maturity-onset adult diabetes subtype（onset>4 years），4 did not have ketotic onset and 2 were treated with metformin alone. A total of 9 INS gene mutations were identified（7 missense，1 splicing and 1 frameshift mutation），including a novel frameshift mutation（c.111dupA，p.Ala38SerfsTer） and the first childhood-onset case with p.Ala2Thr mutation in China. Seven cases were novel mutations，while 4 cases were familial inherited mutations. Six cases with mutations related to B/A chain disulfide bonds（p.Cys43Tyr/p.Cys95Tyr/p.Cys96Tyr/p.Arg89Cys）and a splicing mutation c.188-31G>A had onset in infancy. The onset age varied significantly in individuals with the same mutation（c.188-31G>A），ranging from 7 months to 14 years old. Conclusion　INS gene mutations can lead to two subtypes of adult diabetes：neonatal diabetes and maturity-onset diabetes of the young，exhibiting significant clinical heterogeneity. A novel INS gene mutation c.111dupA is reported in the study. Relatives carrying the same mutation within a family are often misdiagnosed as type 1 or type 2 diabetes. INS gene mutations can cause progressive β-cell dysfunction，highlighting the importance of long-term follow-up monitoring. Treatment strategies should be individualized based on genotype-phenotype characteristics.

Key words: INS gene, monogenic diabetes, neonatal diabetes, maturity-onset diabetes of the young, gene mutation

摘要： 目的　探讨INS基因突变所致儿童单基因糖尿病的临床及遗传学特征，为精准诊疗提供依据。方法　回顾性分析2013年1月至2024年12月南京市儿童医院确诊的11例INS基因突变糖尿病患儿临床资料和基因测序结果，分析基因型与表型关联。结果　11例患儿中男9例、女2例，中位起病年龄0.75岁（0.25~14岁）。6例婴儿期（<1岁）起病者均以酮症或酮症酸中毒首发，依赖胰岛素治疗；5例青少年期（>4岁）起病的成人糖尿病亚型患儿中4例非酮症起病，2例单用二甲双胍治疗。共发现9种INS基因突变（7种错义、1种剪接、1种移码），包括1个新发现移码突变（c.111dupA，p.Ala38SerfsTer）和国内首例儿童期发病的p.Ala2Thr突变。7例为新发突变，4例为家族遗传。6例携带B/A链二硫键相关突变（p.Cys43Tyr/p.Cys95Tyr/p.Cys96Tyr/p.Arg89Cys）及剪接突变c.188-31G>A者婴儿期发病。携带相同突变（c.188-31G>A）在不同个体中发病年龄差异显著（7月龄至14岁）。结论　INS基因突变可导致新生儿糖尿病和青少年起病的成人糖尿病两种亚型，临床表型异质性显著。该研究报道了新的INS基因突变c.111dupA。家系中携带相同突变的亲属常被误诊为1型或2型糖尿病。INS基因突变可导致进行性β细胞功能衰退，强调长期随访监测的重要性，治疗方案应根据基因型-表型特征个体化制定。

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